In the U.S., 5 percent of women over age 60, and 28 percent over age 85 may have dementia. We propose to capitalize on the availability of two large, ongoing randomized trials in women to test interventions for reducing the risk of early cognitive impairment. While advances have been made to delay Alzheimer's disease progression, little research studies the earliest stages of cognitive decline in non-demented women, who might be most susceptible to intervention. Prior investigations have been largely cross-sectional and all observational; no clinical trial data exists. We propose to examine how treatment with aspirin or Vitamin E influences cognitive decline in healthy elderly, and whether antioxidant or folate/B6/B12 supplementation can prevent cognitive dysfunction in women at increased risk of dementia because of their cardiovascular risk factors (and potential ischemic damage in the brain). The investigation will be conducted within the Women's Health Study, a trial of 7,441 healthy women aged 65 years or more randomized to aspirin or Vitamin E for a mean of 4 years as of 1998, and the Women's Antioxidant Cardiovascular Study including 3,445 women aged 65 and older at risk of cardiovascular disease who were randomized to vitamins, E, C, or Beta- carotene for a mean of 2 years as of 1998, and to folate/B6/B12 beginning early 1998. To date, both studies have over 93 percent follow-up and excellent compliance. Information on health status and potential risk factors for cognitive dysfunction is collected on yearly questionnaires. Blood samples were obtained from over 70 percent of participants, allowing us to examine interactions between these treatments and genetic risk factors for dementia, such as the apolipoprotein E4 allele. We will conduct three repeated tests of cognitive function by telephone to all of the women at two-year intervals, using well-established and validated instruments. Pilot testing in 50 participants from both trials has been highly successful; all women have agreed to complete a telephone interview. These two established populations provide a highly cost-efficient manner to investigate interventions, which may delay early decline in cognitive function. Because the trials are on- going, we have only a narrow window of opportunity to implement cognitive testing with adequate follow-up time.